Angiotensin II Modulates Calcium/Phosphate Excretion in Experimental Model of Hypertension: Focus on Bone

Abstract

A link between hypertension and long-term bone health has been suggested. The aim of this study was to investigate the effects of chronic angiotensin II administration on urinary calcium/phosphate excretion, bone mineral density, bone remodeling and osteoblast population in a well-established experimental model of hypertension, in the absence of possible confounding factors that could affect bone metabolism. Male Sprague–Dawley rats, divided in the following groups: (a) Angiotensin II (Ang II, 200 ng/kg/min, osmotic minipumps, sub cutis, n = 8); (b) Ang II+losartan (Los, 50 mg/kg/day, per os, n = 6); (c) control group (physiological saline, sub cutis, n = 9); and (d) control+losartan (n = 6) were treated for four weeks. During the experimental period, 24-hour diuresis, urinary calcium, phosphate and sodium excretion were measured prior to the treatment, at two weeks of treatment, and at the end of the treatment. Systolic blood pressure was measured by plethysmography technique (tail cuff method). At the end of the experimental protocol, the rats were euthanized and peripheral quantitative computed tomography at the proximal metaphysis and at the diaphysis of the tibiae and quantitative bone histomorphometry on distal femora were performed. Angiotensin II-dependent hypertension is associated with increased calcium and phosphate excretion. AT1 receptor blockade prevented the increase of blood pressure and phosphate excretion but did not affect the increase of calcium excretion. These changes took place without significantly affecting bone density, bone histology or osteoblast population. In conclusion, in our experimental conditions, angiotensin II-dependent hypertension gave rise to an increased urinary excretion of calcium and phosphate without affecting bone density.

Concentrations of Transition Metal Ions in Rat Lungs after Tobacco Smoke Exposure and Treatment with His-Leu Dipeptide

“…Exposure to tobacco smoke was carried out for six weeks. Treatment with HL (administered by subcutaneous injection, analogously to angiotensin II administration in other studies [ 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]) started from the third week of exposure to tobacco smoke and lasted four weeks.…”

“…Administering 5 mg HL/kg body weight per day would result in the basal concentration (10 pM) in the whole rat body after about four hours following injection, assuming a 10 min half-life of HL because of the subcutaneous route (in contrast to intravenous injection) and the average rat tissue water content of 65.6% [ 88 ]. Although the chosen dosage may seem relatively low, angiotensin II is administered to rats usually subcutaneously in the concentration range of 0.1–1.5 mg/kg body weight per day, with biological effects observed on the level of the whole organism [ 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Therefore, our choice for dosage is higher than that of angiotensin II (calculating it, one should also consider the difference in molecular weights of these peptides, which means that we administered from 14- to 190-fold higher molar content of HL than angiotensin II administered in other studies).…”

“…Therefore, our choice for dosage is higher than that of angiotensin II (calculating it, one should also consider the difference in molecular weights of these peptides, which means that we administered from 14- to 190-fold higher molar content of HL than angiotensin II administered in other studies). However, we should note that we administered HL once per day, opposite to angiotensin II, which was usually administered constantly using an osmotic mini-pump [ 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ].…”

The Relationship between Renin–Angiotensin–Aldosterone System (RAAS) Activity, Osteoporosis and Estrogen Deficiency in Type 2 Diabetes

“…Moreover, estrogen has been evidenced to mediate the transcription of ACE2; thus ACE2 is downregulated and AT1R is upregulated in estrogen deficiency, leading to estrogen deficiency-induced osteoporosis [174]. Ang II also downregulates the mRNA expression of osteocalcin, which is uniquely produced during the maturation of osteoblastic cells [175]. Additionally, Ang II reduces the activity of alkaline phosphatase (ALP), which is a hallmark of osteoblastic differentiation [175,176].…”

“…Ang II also downregulates the mRNA expression of osteocalcin, which is uniquely produced during the maturation of osteoblastic cells [175]. Additionally, Ang II reduces the activity of alkaline phosphatase (ALP), which is a hallmark of osteoblastic differentiation [175,176]. Thus, estrogen is critical for balancing bone resorption and formation [26,177].…”